Biomarkers Fail to Deliver in Ovarian Cancer Detection


HAMBURG, GERMANY — The combination of four new serum biomarkers did not improve differentiation of adnexal malignancies from benign disease in a study of 83 women, a finding that differs from those of previous studies.

Median concentrations of osteopontin, insulinlike growth factor (IGF)–II, leptin, and prolactin in preoperative serum samples were not significantly different between women with benign ovarian neoplasm and those with ovarian cancer, Dr. Stefano Guerriero said at the World Congress on Ultrasound in Obstetrics and Gynecology.

Ten women were found to have ovarian cancer, and 73 had benign neoplasm.

The diagnostic performance of the biomarkers was also evaluated using a split-point scoring method in which a score of 1 or lower was required for a benign mass and a score of 2 or more indicated cancer.

With this method, the simultaneous evaluation of the four serum protein markers had a sensitivity of 80% and a specificity of just 10%, he said.

The sensitivity was 68% and specificity 40% with the use of only CA 125, a serum biomarker that is widely used to screen women at increased risk for ovarian cancer and to indicate treatment response in those with ovarian cancer.

Transvaginal ultrasonography showed a sensitivity of 80% but a specificity of 92%, reported Dr. Guerriero and his colleagues at the University of Cagliari (Italy).

“Although previously proposed with encouraging results in the screening of ovarian cancer, the preliminary evaluation of these new biomarkers does not seem to be useful in the preoperative evaluation of patients with an adnexal mass when compared with CA 125 and transvaginal ultrasonography,” he said.

In a 2005 blind, cross-validation study, no single marker could completely distinguish women with ovarian cancer from healthy controls, but the combination of the four proteins achieved a striking 95% sensitivity, specificity, and positive predictive value and a negative predictive value of 94% (Proc. Natl. Acad. Sci. USA 2005;102:7677–82). In a more recent study evaluating an ovarian cancer marker panel that included leptin, prolactin, osteopontin, IGF-II, macrophage migration inhibitory factor, and CA 125, only CA 125, osteopontin, and IGF-II levels differed significantly between ovarian cancer patients and controls with benign ovarian disease (Anticancer Res. 2009;29:573–6).

When asked how the studies' findings could be so different, Dr. Guerriero responded that he did not know, adding that his study took considerable time and money to conduct. “It's incredible to me,” he said.

The 10 malignancies in the study included 4 primary invasive tumors (2 stage III and 2 stage IV), 3 borderline tumors, and 3 metastatic cancers (2 breast and 1 stomach). The majority of the benign masses were endometriomas (29), serous masses (15), and dermoid masses (13). The mean age of the cohort was 41 years, and 18% were postmenopausal.

The study was supported by Assessorato Igiene e Sanità, Regione Autonoma della Sardegna.

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